Biomedical subjects

A Dufresne

Publications and source records attributed to A Dufresne.

At least 19 recordsLinked to original sources

PubMed2001

Gamma-ray crosslinking of poly(3-hydroxyoctanoate-co-undecenoate).

The gamma-ray crosslinking of films made of poly(3-hydroxyoctanoate) containing undecenoate moieties (up to 33 mole%) were studied. X-ray diffraction, thermal analysis, dynamic mechanical analysis (DMA), solid state nuclear magnetic resonance (NMR) spectroscopy and degree of crosslinking (swelling analysis) as a function of irradiation dose were evaluated for treatments in air or in N(2) atmosphere. After uncrosslinked material was isolated by CHCl(3) extraction, solid state NMR data suggested that only a small percentage of the double bonds took part in the formation of irradiation crosslinks. Crosslinking in N(2) was more efficient than in air and a 20 kGy dose was sufficient for optimal crosslinking. The X-ray diffraction patterns of the polymer films were unaffected by moderate irradiation. The use of sodium hypochlorite to isolate poly(3-hydroxyoctanoate-co-undecenoate) samples resulted in partial chlorination of the double bonds and considerable depolymerization.

Biocompatible Materials↗

PubMed2001

Excellent therapeutic efficacy and minimal late neurotoxicity in children treated with 18 grays of cranial radiation therapy for high-risk acute lymphoblastic leukemia: a 7-year follow-up study of the Dana-Farber Cancer Institute Consortium Protocol 87-01.

BACKGROUND: In the current study, the authors evaluated late neuropsychologic effects 7 years after diagnosis and the long-term survival in a cohort of patients treated for high-risk childhood acute lymphoblastic leukemia (ALL) with cranial radiation therapy. Efficacy and toxicity were evaluated in relation to patient age at diagnosis (age < or > or = 36 months). METHODS: Two hundred and one patients treated for high-risk ALL on the Dana-Farber Cancer Institute Consortium Protocol 87-01 were included, 147 of whom were in continuous complete disease remission and were eligible for cognitive testing. Sixty-one patients consented to undergo testing. All patients received 18 grays (Gy) of cranial radiation as a component of central nervous system treatment. RESULTS: For all 201 patients, the 5-year overall survival (% +/- the standard error) was 82% +/- 2 and the 5-year event-free survival (% +/- the standard error) was 75% +/- 3. Only two patients developed a central nervous system recurrence. Intelligence quotient (IQ) and memory were at the expected mean for age, but performance on a complex figure drawing task was found to be reduced. Children who were age < 36 months at the time of diagnosis were found to have an IQ in the average range, but showed verbal deficits. CONCLUSIONS: The results of the current study demonstrate excellent efficacy of therapy and relatively limited late neurotoxicity on a childhood ALL therapy protocol in which all evaluated patients had received 18 Gy of cranial radiation. Efficacious therapy that includes cranial radiation does not appear to necessarily incur a heightened risk for significant cognitive impairment.

Adolescent↗

PubMed2000

Risk of respiratory exposure of dental personnel to amalgam alternatives.

Although the use of alternatives to dental amalgam is increasing, the possible hazard associated with their occupational exposure has received inadequate attention. The purpose of this study is to use available toxicological and environmental information in a qualitative risk assessment to address potential health hazards associated with exposure to these materials by dental personnel. The members of dental profession should be aware of risk due to long-term exposure to dental materials.

Dental Amalgam↗

PubMed2000

[Abdominal complications of Crohn's disease: CT features].

Crohn's disease is characterized by transmural inflammation and chronic disorder of the gastrointestinal tract. Abdominal complications of Crohn's disease are frequent and quite variable and their diagnosis is commonly performed with CT. The purpose of this article is to review the CT features of the abdominal complications of Crohn's disease, including ileocolitis, abscess, phlegmon, fistula, bowel obstruction, portal vein gas, colonic distention, as well as urinary, hepatobiliary and pancreatic complications.

Abdominal Abscess↗

PubMed1999

Inferences on the kinetics of asbestos deposition and clearance among chrysotile miners and millers.

BACKGROUND: The health effects of asbestos are intimately related to the fate of inhaled fibers in the lungs. The kinetics of asbestos fibers have been studied primarily in rodents. The objective of this study was to explore the application of these kinetic models to human autopsy data. METHODS: We analyzed the asbestos fiber content of the lungs of 72 Quebec chrysotile miners and millers and 49 control subjects using analytical transmission electron microscopy. Statistical methods included standard multivariate linear regression and locally weighted regression methods. RESULTS: The lung burdens of asbestos bodies and chrysotile and tremolite fibers were correlated, as were the concentrations of short, medium, and long fibers of each asbestos variety. There were significant associations between the duration of occupational exposure and the burdens of chrysotile and tremolite. The concentration of chrysotile decreased with the time since last exposure but the concentration of tremolite did not. The clearance rate varied inversely with the length of chrysotile fibers. For fibers greater than 10 mu in length the clearance half-time was estimated to be 8 years. CONCLUSIONS: The patterns in our data are compatible with both of the hypotheses suggested from rodent experiments; the existence of a long-term sequestration compartment and overload of clearance mechanisms in this compartment.

Aged↗

PubMed1999

Clearance of man made mineral fibres from the lungs of sheep.

OBJECTIVES: To compare the clearance rate, the related pathology, and the chemical and morphological changes of three man made mineral fibres (MMMFs) in the sheep model of pneumoconiosis. METHODS: Fibrous particles were extracted from lung parenchyma and analysed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). RESULTS: The concentration of MMMF11, MMMF21, refractory ceramic fibre (RCF-1), and crocidolite asbestos fibres decreased with time according to a slow and a fast kinetic component. There was a statistical difference in the four regression lines as a function of time and the type of fibres (p < 0.001). The diameter of MMMFs decreased during the course of the time, whereas the crocidolite fibres did not seem to show any change. There was a statistical difference in the four regression lines as a function of time (p = 0.037) and type of fibres (p < 0.001). Ferruginous bodies were counted in the 40 sheep for which the latency period was 2 years. No typical ferruginous bodies were found in the groups exposed to MMMFs. The geometric mean concentration of asbestos bodies in the group exposed to crocidolite was 2421 bodies/g lung tissue (95% CI 385 to 15260). CONCLUSIONS: The number of initially retained fibres decreased with time according to a slow and a fast kinetic component. MMMF11 and MMMF21 have similar clearance, faster than RCF-1 and crocidolite. The geometric mean diameter and length of MMMF decreased with time, but crocidolite did not. After 2 years in the sheep tracheal lobe, ferruginous bodies were not found in all three MMMF groups but were substantial in the crocidolite group. Clearance is thought to proceed through dissolution and macrophage translocation.

Animals↗

PubMed1999

Case-control study of lung cancer among sugar cane farmers in India.

OBJECTIVES: To investigate the risk of lung cancer among sugar cane farmers and sugar mill workers. METHODS: A case-control study was conducted based in six hospitals in the predominantly sugar cane farming districts of the province of Maharashtra in India. Newly diagnosed, histologically confirmed cases were identified from these hospitals between May 1996 and April 1998. Other cancers were chosen as controls and matched to cases by age, sex, district of residence, and timing of diagnosis. RESULTS: Adjusting for confounders, an increased risk of lung cancer was found for workers ever employed on a sugar cane farm (odds ratio (OR) 1.92, 95% confidence interval (95% CI) 1.08 to 3.40). Increased risks were found for work involving preparation of the farm (OR 1.81, 95% CI 0.99 to 3.27) and burning of the farm after harvesting (OR 1.82, 95% CI 0.99 to 3.34). Non-significant increases in risks were found for harvesting the crop (OR 1.41, 95% CI 0.70 to 2.90) and processing the cane in the mills (OR 1.70, 95% CI 0.20 to 12.60). CONCLUSIONS: Exposure to fibres of biogenic amorphous silica (BAS) formed from silica absorbed from the soil and deposited in the leaves of the sugar cane crop or crystalline silica formed as a result of conversion of BAS to cristobalite at high temperatures may account for the increased risks of lung cancer among sugar cane farmers.

Adult↗

PubMed1998

Angular and fibrous particles in lung in relation to silica-induced diseases.

INTRODUCTION: The lung concentration of angular and fibrous particles was measured in cases of lung fibrosis only, in cases of lung fibrosis and lung cancer, and in cases of lung cancer only. These patients worked in different trades (mining, foundries, construction and were not a homogeneous group of exposed workers. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique, and analyzed by transmission electron microscopy (TEM) and energy-dispersive spectroscopy (EDS). The quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after extraction from the lung parenchyma. RESULTS: (1) Lung cancer and lung fibrosis cases retained more metal-rich particles (P = 0.02) and more angular particles of all sorts (P = 0.009) than did lung fibrosis cases only, and the differences were statistically significant. (2) However, more quartz was retained in the lungs in lung fibrosis cases than in lung fibrosis or lung cancer cases, but the difference in the concentrations was not statistically significant. (3) More ferruginous bodies were retained in the lungs in lung cancer and lung fibrosis cases than in cases of lung fibrosis only, and the difference in the concentrations was statistically significant (P = 0.02). CONCLUSION: Results obtained from lung tissue must always be interpreted cautiously. However, these results are consistent with the hypothesis that workers in some trades such as foundries were exposed not only to quartz but also to asbestos, ceramic fibers, metal-rich non fibrous particles, and other likely carcinogenic chemicals. The wide range of particle types identified in the lungs of these workers illustrates the complexity of trying to determine disease origins in these work environments. Epidemiology studies have to control for the exposure to these carcinogens as well as for smoking habits.

Aged↗

PubMed1997

Angular and fibrous particles in lung are markers of job categories.

INTRODUCTION: The lung concentration of angular and fibrous particles has been measured when cases are stratified into their job categories; 21 miners (metallic mines such as gold, zinc and copper), 18 iron foundrymen, 22 non-iron foundrymen, four welders, three sand-blast workers, four construction workers, three technicians and professionals, seven workers in other trades excluding welding. Twelve asbestos miners representing a positive exposure to asbestos and 20 people representing a background population were added to the previous groups. MATERIAL AND METHODS: Particles, both angular and fibrous, were extracted from lung parenchyma by a bleach digestion method, mounted on copper microscopic grids by a carbon replica technique and analyzed by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). Quartz concentration was also determined by X-ray diffraction (XRD) on a silver membrane filter after the extraction from the lung parenchyma. RESULTS: (1) The highest concentrations of quartz were found in mines (metallic mines), iron foundrymen and sand-blast workers. Notable amounts quartz were found in welders and professionals. (2) The highest concentrations of short fibres were found in non-iron foundrymen, asbestos miners and construction workers. (3) The highest concentrations of long fibres were found in non-iron foundry men and asbestos miners. (4) The highest concentrations of ferruginous bodies were found in non-iron foundrymen and asbestos miners. (5) The non-iron foundrymen were exposed to ceramic fibres and asbestos fibres. CONCLUSION: The results of the study may not be representative of the broad spectrum of workers in the industrial activities in which they have been involved. However, the detailed composition of the retained particles of our workers is explained both qualitatively and quantitatively by their work histories. Finally, the broad range of particle types identified in the lungs of these workers illustrate the complexity or trying to determine disease origins in these occupational settings.

Biological Availability↗

PubMed1997

Renal cell carcinoma of clear type: correlation of CT features with tumor size, architectural patterns, and pathologic staging.

The purpose of this study was to report the CT findings of renal cell carcinoma of clear type (RCCCT) and to determine if there are characteristic morphologic features in RCCCT with respect to tumor size, architectural patterns, and pathologic stage. The CT scans of 35 patients with RCCCT were reviewed retrospectively. The CT findings (tumor size, attenuation patterns, presence of calcifications, encapsulation, margins of neoplasms, venous involvement by neoplasms) were correlated with tumor size, architectural patterns, and pathologic staging. Of the 35 neoplasms, 28 (80 %) were solid, 4 (11 %) were papillary, and 3 (9 %) were cystic. Complete encapsulation was more frequent in lower pathologic stages (40 % in stages 1 and 2 vs 0 % in stages 3 and 4; p < 0.05). Venous involvement was less frequent with completely encapsulated neoplasms (0 of 10, 0 %) than with incompletely or nonencapsulated neoplasms (8 of 25, 32 %; p < 0.05). Encapsulated RCCCT are more likely to have lower pathologic stage. Nonencapsulated neoplasms are more likely to have a higher pathologic stage.

Adenocarcinoma, Clear Cell↗

PubMed1997

T1-weighted spoiled gradient-echo MR imaging of focal hepatic lesion: comparison of in-phase vs opposed-phase pulse sequence.

The goal of our prospective study was to compare quantitatively and qualitatively in-phase and opposed-phase T1-weighted breath-hold spoiled gradient-recalled-echo (GRE) MR imaging technique for imaging focal hepatic lesion. Thirty-eight patients with 53 focal hepatic lesions had in-phase (TR = 12.3 ms, TE = 4.2 ms) and opposed-phase (TR = 10.1 ms, TE = 1.9 ms) GRE (flip angle = 30 degrees , bandwidth +/- 32 kHz, matrix size 256 x 128, one signal average) MR imaging at 1.5 T. Images were analyzed quantitatively by measuring the lesion-to-liver contrast and for lesion detection. In addition, images were reviewed qualitatively for lesion conspicuity. Quantitatively, lesion-to-liver contrast obtained with in-phase (3. 22 +/- 1.86) and opposed-phase pulse sequence (3.72 +/- 2.32) were not statistically different (Student's t-test). No difference in sensitivity was found between in-phase and opposed-phase pulse sequence (31 of 53, sensitivity 58 % vs 30 of 53, sensitivity 57 %, respectively). Two lesions not seen with opposed-phase imaging were detected with in-phase imaging. Conversely, one lesion not seen on in-phase imaging was detected on opposed-phase imaging so that the combination of in-phase and opposed-phase imaging yielded detection of 32 of 53 lesions (sensitivity 60 %). Qualitatively, lesion conspicuity was similar with both techniques. However, in-phase images showed better lesion conspicuity than opposed-phase images in 9 cases, and opposed-phase images showed better lesion conspicuity than in-phase images in 7 cases. No definite advantage (at a significant level) emerged between in-phase and opposed-phase spoiled GRE imaging. Because differences in lesion conspicuity and lesion detection may be observed with the two techniques in individual cases, MR evaluation of patients with focal hepatic lesion should include both in-phase and opposed-phase spoiled GRE imaging.

Adult↗

PubMed1997

Mesothelioma in Quebec chrysotile miners and millers: epidemiology and aetiology.

In a cohort of some 11,000 men born 1891-1920 and employed in the Quebec chrysotile production industry, including a small asbestos products factory, of 9780 men who survived into 1936, 8009 are known to have died before 1993, 38 probably from mesothelioma--33 in miners and millers and five in factory workers. Among the 5041 miners and millers at Thetford Mines, there had been 4125 deaths from all causes, including 25 (0.61%) from mesothelioma, a rate of 33.7 per 100,000 subject-years; the corresponding figures for the 4031 men at Asbestos were eight out of 3331 (0.24%, or 13.2 per 100,000 subject-years). At the factory in Asbestos, where all 708 employees were potentially exposed to crocidolite and/or amosite, there were 553 deaths, of which five (0.90%) were due to mesothelioma; the rate of 46.2 per 100,000 subject-years was 3.5 times higher than among the local miners and millers. Six of the 33 cases in miners and millers were in men employed from 2 to 5 years and who might have been exposed to asbestos elsewhere; otherwise, the 22 cases at Thetford were in men employed 20 years or more and the five at Asbestos for at least 30 years. The cases at Thetford were more common in miners than in millers, whereas those at. Asbestos were all in millers. Within Thetford Mines, case-referent analyses showed a substantially increased risk associated with years of employment in a circumscribed group of five mines (Area A), but not in a peripherally distributed group of ten mines (Area B); nor was the risk related to years employed at Asbestos, either at the mine and mill or at the factory. There was no indication that risks were affected by the level of dust exposure. A similar pattern in the prevalence of pleural calcification had been observed at Thetford Mines in the 1970s. These geographical differences, both within the Thetford region and between it and Asbestos, suggest that the explanation is mineralogical. Lung tissue analyses showed that the concentration of tremolite fibres was much higher in Area A than in Area B, a finding compatible with geological knowledge of the region. These findings, probably related to the far greater biopersistence of amphibole fibres than chrysotile, have important implications in the control of asbestos related disease and for wider aspects of fibre toxicology.

Aged↗

PubMed1997

Asbestos, asbestosis, and lung cancer: observations in Quebec chrysotile workers.

One prospective epidemiologic study of asbestos cement workers with radiological small opacities has been cited as a rationale for attributing excess lung cancer to asbestosis. This approach could have considerable practical value for disease attribution in an era of decreasing exposure. However, a recent International Agency for Research on Cancer review concludes that the mechanism of production of asbestos-related lung cancer are unknown. Asbestosis, therefore, cannot be a biologically effective dose marker of lung cancer susceptibility. Asbestosis nonetheless would be useful in identifying asbestos-attributable lung cancer cases if it could be proven an infallible exposure indicator. In this study, we tested this hypothesis in the chrysotile miners and millers of Quebec, Canada. We examined exposure histories, autopsy records, and lung fiber content for 111 Quebec chrysotile miners and millers. If the hypothesis of an asbestosis requirement for lung cancer attribution were accurate, we would expect as asbestosis diagnosis to separate those with lung cancer and high levels of exposure from those with lower levels of exposure in a specific and sensitive manner. This is the first such study in which historical job-based individual estimates based on environmental measurements, lung fiber content, exposure timing, and complete pathology records including autopsies were available for review. We found significant excesses of lung tremolite and chrysotile and estimated cumulative exposure in those with lung cancer and asbestosis compared to those with lung cancer without asbestosis. However, when the latter were directly compared on a case-by-case basis, there was a marked overlap between lung cancer cases with and without asbestosis regardless of the measure of exposure. Smoking habits did not differ between lung cancer cases with and without asbestosis. In regression models, smoking pack-years discriminated between those with the without lung cancer, regardless of asbestosis status. Most seriously, the pathologic diagnosis of asbestosis itself seemed arbitrary in many cases. We conclude that although the presence of pathologically diagnosed asbestosis is a useful marker of exposure, the absence of this disease must be regarded as one of many factors in determining individual exposure status and disease causation.

Aged↗

PubMed1996

Left and right visual field advantages are a function of scotopic and photopic retinal adaptation, respectively, in simple reaction time to near-threshold targets.

Modulation of stimulus luminance in a tachistoscopic face discrimination task has been found to significantly invert visual hemifield advantage in reaction time (RT) (Sergent, 1982a, Sergent, 1982b). However, there is no more physiological rationale for that than for a similar effect, say, of retinal adaptation, and it is even conceivable that the latter may have confounded the former in past experiments. The experiments reported here were therefore designed to tease out the relative contributions of stimulus luminance and of background illumination (i.e., retinal adaptation) in a simple RT task. Two equally difficult conditions of dim targets were set up, one with light-adapted subjects and one with dark-adapted subjects. Similarly, two equally difficult conditions of bright targets were set up with light and dark-adapted subjects. It was found that dim targets (near detection threshold) yielded a significant right visual field RT advantage in light-adapted subjects and that dim targets (equally near detection threshold) yielded a significant left visual field RT advantage in dark-adapted subjects. Future experiments will determine whether cone-mediated RT to detection is left hemisphere dominant and whether rod-mediated RT to detection is right hemisphere dominant.

Adaptation, Ocular↗

PubMed1996

Inorganic particles in the lungs of five aluminum smelter workers with pleuro-pulmonary cancer.

This paper reports on the inorganic particles in the lungs of four workers who died from lung cancer and one who died from mesothelioma. All five workers were involved in different operations and activities in aluminum reduction plants. Retained fibrous and nonfibrous particles were evaluated by transmission electron microscopy and energy dispersive spectroscopy after lung digestion. Asbestos fibers, fragments of silicates, and metal-rich nonfibrous particles of chromium-cobalt and aluminum were detected. Conclusions drawn from the evaluation of the particles retained in the lungs of only five workers must be cautious. However, these results are consistent with the hypothesis that carcinogenic polycyclic aromatic hydrocarbons may not be the only contaminants that could explain excess mortality from malignant lung neoplasm in aluminum smelter workers.

Adult↗

PubMed1996

Retention of asbestos fibres in lungs of workers with asbestosis, asbestosis and lung cancer, and mesothelioma in Asbestos township.

OBJECTIVE: To conduct a mineralogical study on the particles retained in the necropsied lungs of a homogenous group of asbestos miners and millers from Asbestos township (and a local reference population) and to consider the hypothesis that there is a difference in size between fibres retained in the lungs of patients with asbestosis with and without lung cancer. METHODS: Samples of lung tissue were obtained from 38 patients with asbestosis without lung cancer, 25 with asbestosis and lung cancer, and 12 with mesothelioma, from necropsied Quebec chrysotile miners and millers from Asbestos township. Fibre concentrations in the lungs of these patients were compared with those in tissue from necropsies carried out on a local reference population: men who had died of either accidental death or acute myocardial infarction between 1990 and 1992. 23 were born before 1940 and 26 after 1940. RESULTS: Geometric mean (GM) concentrations were higher in cases than in the controls for chrysotile fibres 5 to 10 microns long in patients with asbestosis with or without lung cancer; for tremolite fibres 5 to 10 microns long in all patients; for crocidolite, talc, or anthophyllite fibres 5 to 10 microns long in patients with mesothelioma; for chrysotile and tremolite fibres > or = 10 microns long in patients with asbestosis; and crocidolite, talc, or anthophyllite fibres > or = 10 microns long in patients with mesothelioma. However, median concentrations of each type of fibre in the lungs did not show any significant differences between the three disease groups. Average length to diameter ratios of the fibres were calculated to be larger in patients with asbestosis and lung cancer than in those without lung cancer for crocidolite fibres > or = 10 microns long, for chrysotile, amosite, and tremolite fibres 5 to 10 microns long, and for chrysotile and crocidolite fibres < 5 microns long. However, there was no statistical difference in the median length to diameter ratios for any type of fibres across the disease groups when they were calculated in each patient. Cumulative smoking index (pack-years) was higher in the group with asbestosis and lung cancer but was not statistically different from the two other disease groups. CONCLUSION: Lung cancers occurred in workers with asbestosis from Asbestos township who had an equal concentration of retained fibres but a tendency to a higher length to diameter ratio of amphiboles. These workers had a 29% higher average cumulative smoking index.

Adult↗

PubMed1996

Mineral fiber content of lungs in patients with mesothelioma seeking compensation in Québec.

Asbestos fibers (AF) and ferruginous bodies (FB) in lung parenchyma from 50 workers seeking compensation from the Workers' Compensation Board of Québec for pleural or peritoneal mesothelioma were analyzed using transmission electron microscopy (TEM) equipped with energy-dispersive spectrometer (EDS) and phase-contrast microscopy (PCM). These workers had been occupationally exposed in mining and milling activities (12 were from Asbestos Township and 11 from Thetford Mines) and 27 were from other types of industry (asbestos factory, shipyard, etc.). For comparison, analyses of lung tissue at autopsy were done in a group of 49 subjects from a reference population. A 95% confidence interval upper limit of 540 AF < 5 microns/mg and a 95% confidence interval upper limit of 161 AF > or = 5 microns/mg dried lung tissue were found for the reference population. Similarly, a concentration of FB of 142 FB/g constituted the upper limit of detectable FB in the lungs of the reference population. Forty-eight of the 50 workers with mesothelioma had either a ferruginous body or total asbestos fiber count greater than the 95% confidence interval for the reference population; the remaining two had amosite and/or crocidolite concentrations greater than the 95% confidence interval for the reference population. The fiber types were different in the three groups, with the lungs of workers from Thetford Mines containing only chrysotile and tremolite, those from Asbestos Township containing chrysotile, tremolite, amosite, and crocidolite, and those in other industries containing largely amosite and crocidolite. We conclude that in this population of workers seeking compensation for mesothelioma, fiber analysis confirmed occupational asbestos exposure in every case. The fiber types responsible for the tumors are probably different in the three different groups.

Aged↗

PubMed1996

Transforming growth factor-beta (TGF-beta) in silicosis.

Silicosis is characterized by fibrosing nodular lesions that may eventually develop into progressive massive fibrosis (PMF). Cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor-alpha [TNF-alpha] and growth factors insulin-like growth factor-1 [IGF-1] platelet-derived growth factor [PDGF]) have been implicated in the formation of these lesions. TGF-beta promotes extracellular matrix accumulation by upregulating collagen and fibronectin gene expression, and inhibits matrix degradation by decreasing secretion of proteases and increasing secretion of protease inhibitors. We hypothesized that TGF-beta is associated with matrix deposition and fibrosis in silicosis. To test this hypothesis we studied early and late nodular lesions and PMF (11 cases and two controls) with immunohistochemistry, using rabbit polyclonal antibody to the purified whole molecule of TGF-beta in Bouin's fixed lung tissue. This antibody is reactive with both intra- and extracellular forms of TGF-beta. In the control lungs, small amounts of TGF-beta were present in the bronchial epithelium, macrophages, bronchial and vascular smooth muscle, and bronchial glands. There was minimal to moderate staining in the early silicotic peribronchiolar lesions. In the nodular lesions of silicosis, central hyalinized areas contained the maximum staining for TGF-beta. Fibroblasts in the periphery of the nodular lesions were also positive. In acute silicosis, there was marked staining of hyperplastic alveolar epithelium. Macrophages were markedly positive. In the PMF lesions, large areas of scar tissue contained TGF-beta. These data suggest a major role for TGF-beta in silicosis, particularly in the formation of silicotic nodules and the development of PMF.

Adult↗